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La hemorragia por várices gástricas suele ser más severa y mortal que la causada por várices esofágicas. La terapia vascular guiada por ultrasonido endoscópico (TV-USE) ha demostrado ser un método eficaz y seguro con baja tasa de recurrencia en el tratamiento de la hemorragia por várices gástricas. Se presenta el caso de un paciente con hemorragia causada por una várice gástrica de 3 cm de diámetro quien recibió TV-USE combinada con coil y cianoacrilato con la intención de mostrar las ventajas de la TV-USE combinada.

Background: With the rapid advancement of artificial intelligence (AI) in various fields, evaluating its application in specialized medical contexts becomes crucial. ChatGPT, a large language model developed by OpenAI, has shown potential in diverse applications, including medicine., Objective: This study aims to compare the performance of ChatGPT with that of attending neurologists in a real neurology specialist examination conducted in the Valencian Community, Spain, assessing the AI's capabilities and limitations in medical knowledge., Methods: We conducted a comparative analysis using the 2022 neurology specialist examination results from 120 neurologists and responses generated by ChatGPT versions 3.5 and 4. The examination consisted of 80 multiple-choice questions, with a focus on clinical neurology and health legislation. Questions were classified according to Bloom's Taxonomy. Statistical analysis of performance, including the κ coefficient for response consistency, was performed., Results: Human participants exhibited a median score of 5.91 (IQR: 4.93-6.76), with 32 neurologists failing to pass. ChatGPT-3.5 ranked 116th out of 122, answering 54.5% of questions correctly (score 3.94). ChatGPT-4 showed marked improvement, ranking 17th with 81.8% of correct answers (score 7.57), surpassing several human specialists. No significant variations were observed in the performance on lower-order questions versus higher-order questions. Additionally, ChatGPT-4 demonstrated increased interrater reliability, as reflected by a higher κ coefficient of 0.73, compared to ChatGPT-3.5's coefficient of 0.69., Conclusions: This study underscores the evolving capabilities of AI in medical knowledge assessment, particularly in specialized fields. ChatGPT-4's performance, outperforming the median score of human participants in a rigorous neurology examination, represents a significant milestone in AI development, suggesting its potential as an effective tool in specialized medical education and assessment., (© Pablo Ros-Arlanzón, Angel Perez-Sempere. Originally published in JMIR Medical Education (https://mededu.jmir.org).)

In the second edition of this Special Issue, several promising antitumor strategies have been presented in addition to those reported in the first edition, in which several compounds (acetylcorynoline, BaP1, sarco/endoplasmic reticulum calcium ATPase inhibitors, neuropeptide Y, neuropeptide Y antagonists, neurokinin-1 receptor antagonists) exerting antitumor effects against colorectal cancer, papillary thyroid carcinoma, cholangiocarcinoma, Ewing sarcoma, liver cancer, and breast cancer were reported [...].

The present systematic review aims to identify electronic interventions for addressing substance use and understand their effectiveness in primary care settings. A systematic search was carried out in the Web of Science, PubMed/MEDLINE, Scopus, and Cochrane Library. The search included the keywords "electronic intervention", "substance use", "primary care" and synonyms. To determine the quality and recommendation of the analyzed interventions, the efficacy results reported by the studies were considered, as well as the Mixed Methods Appraisal Tool (MMAT) assessment and the GRADE Evidence Assessment. Twenty-one electronic interventions in Primary Care were identified: internet, mobile or tablet applications, text messages, emails, automated telephone calls, or electronic self-reports. These interventions had diverse components, incorporating theories that have proven effective in face-to-face interventions as their theoretical frameworks. Some of them were complementary to in-person treatment, while others replaced it. Six interventions (28.5 %) displayed high quality: HealthCall, AB-CASI, Quit Genius, eCHECKUP-TOGO, CBI, and TES. Another nine interventions (42.8 %) were found to have moderate-high quality: Alcohol y Salud, IVR-BI, Program of Wallace et al., Let's Talk About Smoking, SMSalud, ESCAPE, AAC-ASPIRE, iQuit, and Programa VIH. One intervention (4.7 %) had moderate-low quality: Vive sin tabaco ¡Decídete! The remaining five interventions (23.8 %) were found to have very low quality: Connection to health, cSBI, Teen Well Check, the program of Helzer et al. (2008), and Down your drink. The programs with the highest recommendation for addressing alcohol-related issues are HealthCall and AB-CASI; for tobacco use, it is Quit Genius; for cannabis use, it is eCHECKUP-TOGO; for addressing both legal and illegal substances, it is CBI and TES. Finally, for specific illicit drug use, the only recommended program is CBI. This last intervention, CBI, is of the highest quality and, therefore, can be considered a model intervention for dissemination in the primary care setting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Villanueva-Blasco reports financial support was provided by Research Network in Primary Addiction Care (RIAPAd). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes., Materials and Methods: An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded., Results: The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present., Conclusion: The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Horses are often still exposed to stressful or inadequate conditions and difficult relationships with humans, despite growing concerns about animal welfare. In the present study, we investigated the impact of different approaches of short-term handling sessions on young Lusitanian horses raised on a high-breed farm, specifically on their later adaptability to humans and stressful environments. Thirty-one foals (3 months old ± 15 days), from both sexes, were separated into three groups, one submitted to 3 consecutive days of handling sessions (Int-H), another to one handling session each month for 3 months (Month-H), and one left undisturbed (control). At 8 months old ± 15 days, all foals were evaluated during behavioral tests (restraint in a stock and forced-person test). Evaluations were based on behavioral observations and physiological assessments. The handled foals (Int-H and Month-H) reacted less to being isolated and restrained and better tolerated human contact and veterinary procedures than the control ones. The handled foals displayed less evasive and negative behaviors toward human approach, but also sought less human contact and did not interact, regardless of the handling timeframe. All animals displayed signs of stress when restrained in the stock, with increased neutrophil counts and CHCM levels in the blood, and no differences in metabolic (CK and LDH) and other hematological parameters. The neutrophil-lymphocyte ratio was significantly higher ( p < 0.05) in handled foals than in control ones, suggesting low standards of welfare. Our data suggest that early forced handling decreases fearfulness in new environments; however, it does not improve the horses' relationship with humans, and it decreases welfare.

Background: Myeloid-derived suppressor cells (MDSCs) constitute a recently discovered bone-marrow-derived cell type useful for dealing with neuroinflammatory disorders. However, these cells are only formed during inflammatory conditions from immature myeloid cells (IMCs) that acquire immunosuppressive activity, thus being commonly gathered from diseased animals. Then, to obtain a more clinically feasible source, we characterized IMCs directly derived from healthy bone marrow and proved their potential immunosuppressive activity under pathological conditions in vitro. We then explored their neuroprotective potential in a model of human cerebellar ataxia, the Purkinje Cell Degeneration (PCD) mouse, as it displays a well-defined neurodegenerative and neuroinflammatory process that can be also aggravated by invasive surgeries., Methods: IMCs were obtained from healthy bone marrow and co-cultured with activated T cells. The proliferation and apoptotic rate of the later were analyzed with Tag-it Violet. For in vivo studies, IMCs were transplanted by stereotactic surgery into the cerebellum of PCD mice. We also used sham-operated animals as controls of the surgical effects, as well as their untreated counterparts. Motor behavior of mice was assessed by rotarod test. The Purkinje cell density was measured by immunohistochemistry and cell death assessed with the TUNEL technique. We also analyzed the microglial phenotype by immunofluorescence and the expression pattern of inflammation-related genes by qPCR. Parametric tests were applied depending on the specific experiment: one or two way ANOVA and Student's T test., Results: IMCs were proven to effectively acquire immunosuppressive activity under pathological conditions in vitro, thus acting as MDSCs. Concerning in vivo studios, sham-operated PCD mice suffered detrimental effects in motor coordination, Purkinje cell survival and microglial activation. After intracranial administration of IMCs into the cerebellum of PCD mice, no special benefits were detected in the transplanted animals when compared to untreated mice. Nonetheless, this transplant almost completely prevented the impairments caused by the surgery in PCD mice, probably by the modulation of the inflammatory patterns., Conclusions: Our work comprise two main translational findings: (1) IMCs can be directly used as they behave as MDSCs under pathological conditions, thus avoiding their gathering from diseased subjects; (2) IMCs are promising adjuvants when performing neurosurgery., (© 2024. The Author(s).)

Introduction: Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources., Objective: To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID., Methods: This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2 , ABCB1 , and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications., Results: The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases., Conclusion: A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.

Introduction: Atrial fibrillation (AF) is the main cause of cardioembolic stroke. In high-bleeding-risk patients, long-life anticoagulation therapy is not permitted, and left atrial appendage (LAA) closure may be considered. LAA is also a critical substrate for AF. Epicardial LAA occlusion has several advantages: LAA ligation results in a favorable electrical and structural atrial remodeling, which decreases AF recurrence. Endocardial ablation alone is not efficient for all patients, and new evidence shows better outcomes in patients affected by persistent AF after a combined hybrid endo-epicardial ablation. Considering the synergic potential of these techniques, in this case series, they were both combined in a single procedure., Methods and Results: We describe the treatment of 5 patients referred for refractory AF ablation and LAA closure. All patients had high thrombotic and previous major hemorrhage, with relative contraindication to life-long therapy with anticoagulation. A combined procedure of LAA ligation and endo-epicardial ablation was scheduled with short-term anticoagulation. LAA closure was performed with an epicardial approach using the LARIAT system. Then, LA mapping and ablation were performed, endocardially and then epicardially.All procedures were concluded without complications.At follow-up, in all patients, transesophageal echocardiography showed the complete occlusion of the LAA; therefore, anticoagulation therapy was interrupted. All patients were asymptomatic, and in the sinus rhythm, no hemorrhage or ischemic events occurred., Conclusion: The combination of percutaneous LAA ligation and endo-epicardial ablation was revealed to be feasible and safe and might represent a new approach for the treatment of refractory AF in patients with indication of LAA occlusion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Grossi, Bianchi, Blandino, Pintor, Tomasello, Mabritto and Musumeci.)

One interesting strategy to address the increasing alcohol content of wines, associated with climate change, is to reduce the ethanol yield during fermentation. Within this strategy, the approach that would allow the clearest reduction in alcohol content is the respiration of part of the grape sugars by yeasts. Non-Saccharomyces species can be used for this purpose but suffer from a limited ability to dominate the process and complete fermentation. In turn, Saccharomyces cerevisiae shows a high production of acetic acid under the growth conditions required for respiration. Previously proposed procedures used combinations of non-Saccharomyces and S. cerevisiae starters, or a strain of S. cerevisiae (PR1018), with unique metabolic properties. In both cases, precise management of oxygen availability was required to overcome the acetic acid problem. In this work, we have developed a laboratory scale process to take advantage of the properties of PR1018 and a strain of Metschnikowia pulcherrima. This process is more robust than the previous ones and does not rely on strict control of oxygenation or even the use of this particular strain of S. cerevisiae. Aeration can be interrupted instantly without impairing the volatile acidity. Under the selected conditions, an ethanol reduction of around 3% (v/v) was obtained compared to the standard fermentation control., Competing Interests: Declaration of competing interest The authors of this manuscript declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The performance of first-year students in electromagnetism (E&M) courses of different engineering degrees at a Spanish public university was measured using the Brief Electricity and Magnetism Assessment (BEMA), a standard research-based instrument to assess students' understanding after attending introductory courses in electricity and magnetism. In all cases, Flipped classroom (FC) built on information and communications technology was used. The objective of this paper is to analyse if the gain in the BEMA pre and post-test results is influenced by several factors such as the degree, the students' academic grade, and gender. Moreover, as some studies have shown that the students' retention of the concepts was significantly stronger in active learning than in traditional approaches, a third BEMA test was performed by the students to analyse the long-term retention gain dependence on the same factors. Students from different engineering degree programs were asked to complete two BEMA tests during the course and a third one after a few months. ANOVA tests were used to analyse the existence of significant differences in gain between student degree programs, student academic level and student gender. Results have shown no differences in the BEMA performance by degree program, but significant differences were found by academic level and gender. Retention did not depend on the degree course but on the academic level. Mean gain value by academic level, and gender was obtained and concluded that the best students presented the best gain results and that gain depends on the students' gender: males outperformed females in the BEMA tests, although there were no significant differences in the course grades. It is thus necessary to understand these differences and to implement measures in daily teaching work to improve women's performance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

The use of yeast respiratory metabolism has been proposed as a promising approach to solve the problem of increasing ethanol content in wine, which is largely due to climate change. The use of S. cerevisiae for this purpose is mostly hampered by acetic acid overproduction generated under the necessary aerobic conditions. However, it was previously shown that a reg1 mutant, alleviated for carbon catabolite repression (CCR), showed low acetic acid production under aerobic conditions. In this work directed evolution of three wine yeast strains was performed to recover CCR-alleviated strains, expecting they will also be improved concerning volatile acidity. This was done by subculturing strains on galactose, in the presence of 2-deoxyglucose for around 140 generations. As expected, all evolved yeast populations released less acetic acid than their parental strains in grape juice, under aerobic conditions. Single clones were isolated from the evolved populations, either directly or after one cycle of aerobic fermentation. Only some clones from one of three original strains showed lower acetic acid production than their parental strain. Most clones isolated from EC1118 showed slower growth. However, even the most promising clones failed to reduce acetic acid production under aerobic conditions in bioreactors. Therefore, despite the concept of selecting low acetic acid producers by using 2-deoxyglucose as selective agent was found to be correct, especially at the population level, the recovery of strains with potential industrial utility by this experimental approach remains a challenge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Inflammatory bowel diseases (IBD) are chronic diseases, encompassing Crohn's disease (CD) and ulcerative colitis (UC). An IBD diagnosis has an impact on the quality of life of patients; this impact can be different according to the type of disease., Objective: This study aimed to analyze the differences in the impact on quality of life in the early stages after diagnosis in patients with CD and UC., Patients and Methods: This was an observational, multi-center, and cross-sectional study, with the participation of 156 patients recently diagnosed with IBD (<6 months) from 4 hospitals from the Health Council of the Valencian Community. The patients were assessed through the use of the Inflammatory Bowel Disease Questionnaire (IBDQ-32), which measures the quality of life when living with IBD., Results: The sample was composed of 80 patients with CD (51.0%) and 76 patients with a UC diagnosis. The mean age was 42.3 ± 16.2. The CD patients were more affected (42.5%) in their general quality of life than the UC patients (17.1%) ( p = 0.001). In the dimensions of the IBDQ-32, the patients with CD showed significant differences in the systemic, emotional, and social spheres. The bowel dimension scores were similar in both groups., Conclusions: The patients who were recently diagnosed with CD were more affected regarding their quality of life as compared to those who were diagnosed with UC. Psychological care must be considered to mitigate the impact of an IBD diagnosis.

Lichens thrive in rocky coastal areas in temperate and cold regions of both hemispheres. Species of the genus Lichina, which form characteristic black fruiting thalli associated with cyanobacteria, often create distinguishable bands in the intertidal and supralittoral zones. The present study uses a comprehensive specimen dataset and four gene loci to (1) delineate and discuss species boundaries in this genus, (2) assess evolutionary relationships among species, and (3) infer the most likely causes of their current geographic distribution in the Northern and Southern hemispheres. A dated phylogeny describes the time frame in which extant disjunctions of species and populations were established. The results showed that the genus is integrated by four species, with Lichina pygmaea, L. confinis and the newly described L. canariensis from rocky seashores in the Canary Islands, occurring in the Northern Hemisphere, whereas L. intermedia is restricted to the Southern Hemisphere. Lichina intermedia hosted a much higher intraspecific genetic diversity than the other species, with subclades interpreted as species-level lineages by the different species delimitation approaches. However, a conservative taxonomic approach was adopted. This species showed a striking disjunct distribution between Australasia and southern South America. The timing for the observed interspecific and intraspecific divergences and population disjunctions postdated continental plate movements, suggesting that long-distance dispersal across body waters in the two hemispheres played a major role in shaping the current species distributions. Such ocean crossings were, as in L. canariensis, followed by speciation. New substitution rates for the nrITS of the genus Lichina were inferred using a tree spanning the major Ascomycota lineages calibrated using fossils. In conclusion, this work lays the foundation for a better understanding of the evolution through time and space of maritime lichens., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Multiclass screening methods involving hundreds of structurally unrelated compounds are becoming essential in many control labs and research areas. Accurate mass screening of a theoretically unlimited number of chemicals can be undertaken using liquid chromatography coupled to high resolution mass spectrometry (LCHRMS), but the lack of comprehensive sample treatments hinders this unlimited potential. In this research, the capability of supramolecular solvents (SUPRAS) for making comprehensive liquid-liquid microextraction (LLME) in multiclass screening methods based on LCHRMS was firstly explored. For this purpose, a SUPRAS made up of 1,2-hexanediol, sodium sulphate and water was synthesized directly in the urine and applied to compound extraction and interference removal in the screening of eighty prohibited substances in sports by LC-electrospray ionization-time of flight mass spectrometry. Selected substances included a wide range of polarities (log P from -2.4 to 9.2) and functionalities (e.g. alcohol, amine, amide, carboxyl, ether, ester, ketone, sulfonyl, etc.). No interfering peaks were observed for any of the 80 substances investigated. Around 84-93% of drugs were efficiently extracted (recoveries 70-120%) and 83-94% of the analytes did not show matrix effects (±20%) in the ten tested urines. Method detection limits for the drugs were in the interval 0.002-12.9 ng mL -1 , which are in accordance with the Minimum Required Performance Levels values established by the World Anti-Doping Agency. The applicability of the method was evaluated by the screening of thirty-six blinded and anonymized urine samples, previously analyzed by gas or liquid chromatography-triple quadrupole. Seven of the samples lead to an adverse analytical finding in line with the results obtained by the conventional methods. This research proves that LLME based on SUPRAS constitutes an efficient, economic, and simple sample treatment in multiclass screening methods, an application that is unaffordable for conventional organic solvents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interest or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients ( n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6 , μ-opioid receptor ( OPRM1 ), and catechol-O-methyl transferase ( COMT ) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1-5] vs. 1 [0-2], p < 0.01) and 42% opioid dose (35 [22-61] vs. 60 [40-80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58-0.82] vs. 0.51 [0.13-0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30-34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.

Vegetarian and vegan diets are increasingly being adopted in Spain, a trend mainly driven by ethical concerns for animal welfare and the environment. This has resulted in a growing market for plant-based substitutes of meat products. However, available data on the nutritional value of such meat analogues in Mediterranean countries are still limited. In this study, the labelling information of four categories of plant-based meat analogues ( n = 100) and the corresponding conventional meat products ( n = 48) available on the Spanish market was surveyed and compared. The nutrient content of plant-based meat analogues varied significantly, due to the wide range of ingredients used in their formulation. Some of these products were found to have a low protein content, which in others was enhanced by the addition of cereals and legumes. Compared to the meat products, the plant-based analogues contained lower levels of total fat as well as saturated fat, which ranged from 30% of total fat in burgers to less than 15% in meatballs, sausages, and nuggets; in contrast, they contained higher amounts of fiber and complex carbohydrates. Overall, the meat analogues cannot be considered as nutritionally equivalent substitutes to conventional meat products due to a high variability of protein content and other nutrients.

More than half of patients with opioid use disorder for chronic non-cancer pain (CNCP) reduced their dose through a progressive opioid withdrawal supported by a rotation to buprenorphine and/or tramadol. The aim of this research is to analyse the long-term effectiveness of opioid deprescription taking into account the impact of sex and pharmacogenetics on the inter-individual variability. A cross-sectional study was carried out from October 2019 to June 2020 on CNCP patients who had previously undergone an opioid deprescription ( n = 119 patients). Demographic, clinical (pain, relief and adverse events) and therapeutic (analgesic use) outcomes were collected. Effectiveness (< 50 mg per day of morphine equivalent daily dose without any aberrant opioid use behaviour) and safety (number of side-effects) were analysed in relation to sex differences and pharmacogenetic markers impact [ OPRM1 genotype (rs1799971) and CYP2D6 phenotypes]. Long-term opioid deprescription was achieved in 49 % of the patients with an increase in pain relief and a reduction of adverse events. CYP2D6 poor metabolizers showed the lowest long-term opioid doses. Here, women showed a higher degree of opioid deprescription, but increased use of tramadol and neuromodulators, as well as an increased number of adverse events. Long-term deprescription was successful in half of the cases. Understanding sex and gender interaction plus a genetic impact could help to design more individualized strategies for opioid deprescription., (© 2023 Javier Muriel et al., published by Sciendo.)

Analgesic-response variability in chronic noncancer pain (CNCP) has been reported due to several biological and environmental factors. This study was undertaken to explore sex differences linked to OPRM1 and COMT DNA methylation changes and genetic variants in analgesic response. A retrospective study with 250 real-world CNCP outpatients was performed in which data from demographic, clinical, and pharmacological variables were collected. DNA methylation levels (CpG island) were evaluated by pyrosequencing, and their interaction with the OPRM1 (A118G) and COMT (G472A) gene polymorphisms was studied. A priori-planned statistical analyses were conducted to compare responses between females and males. Sex-differential OPRM1 DNA methylation was observed to be linked to lower opioid use disorder (OUD) cases for females ( p = 0.006). Patients with lower OPRM1 DNA methylation and the presence of the mutant G-allele reduced opioid dose requirements ( p = 0.001), equal for both sexes. Moreover, COMT DNA methylation levels were negatively related to pain relief ( p = 0.020), quality of life ( p = 0.046), and some adverse events (probability > 90%) such as constipation, insomnia, or nervousness. Females were, significantly, 5 years older with high anxiety levels and a different side-effects distribution than males. The analyses demonstrated significant differences between females and males related to OPRM1 signalling efficiency and OUD, with a genetic-epigenetic interaction in opioid requirements. These findings support the importance of sex as a biological variable to be factored into chronic pain-management studies.

Harmful alcohol use is responsible for a group of disorders collectively named alcohol use disorders (AUDs), according to the DSM-5 classification. The damage induced by alcohol depends on the amount, time, and consumption patterns (continuous and heavy episodic drinking). It affects individual global well-being and social and familial environments with variable impact. Alcohol addiction manifests with different degrees of organ and mental health detriment for the individual, exhibiting two main traits: compulsive drinking and negative emotional states occurring at withdrawal, frequently causing relapse episodes. Numerous individual and living conditions, including the concomitant use of other psychoactive substances, lie in the complexity of AUD. Ethanol and its metabolites directly impact the tissues and may cause local damage or alter the homeostasis of brain neurotransmission, immunity scaffolding, or cell repair biochemical pathways. Brain modulator and neurotransmitter-assembled neurocircuitries govern reward, reinforcement, social interaction, and consumption of alcohol behaviors in an intertwined manner. Experimental evidence supports the participation of neurotensin (NT) in preclinical models of alcohol addiction. For example, NT neurons in the central nucleus of the amygdala projecting to the parabrachial nucleus strengthen alcohol consumption and preference. In addition, the levels of NT in the frontal cortex were found to be lower in rats bred to prefer alcohol to water in a free alcohol-water choice compared to wild-type animals. NT receptors 1 and 2 seem to be involved in alcohol consumption and alcohol effects in several models of knockout mice. This review aims to present an updated picture of the role of NT systems in alcohol addiction and the possible use of nonpeptide ligands modulating the activity of the NT system, applied to experimental animal models of harmful drinking behavior mimicking alcohol addiction leading to health ruin in humans.

Knowing the frequency and characteristics of adverse events (AEs) is key to implementing actions that can prevent their occurrence. However, reporting systems are insufficient for this purpose and epidemiological studies are also required. Currently, the reviewing of clinical records is the gold standard method for knowing the frequency and characteristics of AEs. Research on AEs in a primary care setting has been limited and primarily focuses on specific types of events (medication errors, etc.) or patients. Large studies that search for any kind of AE in all patients are scarce. This study aimed to estimate the prevalence of AEs in the primary care setting and their characteristics., Setting: all 262 primary health-care centres in the Madrid region (Spain) during the last quarter of 2018., Design: cross-sectional descriptive study. Eligible population: subjects over 18 years of age who attended medical consultation over the last year (N = 2 743 719); a randomized sample stratified by age., Main Outcomes: age, sex, occurrence of an AE, number of consultations in the study period, avoidability, severity, place of occurrence, type of event, and contributory factors. The clinical records were reviewed by three teams, each composed of one doctor and one nurse trained and with expertise in patient safety. The SPSS software package (version 26) was used for the statistical analyses. The evaluators reviewed 1797 clinical records. The prevalence of AEs over the study period was 5.0% [95% confidence interval (CI): 4.0%‒6.0%], with higher values in women (5.7%; 95% CI: 4.6%‒6.8%;P = 0.10) and patients over 75 years of age (10.3%; 95% CI: 8.9%‒11.7%; P < 0.001). The overall occurrence per hundred consultations was estimated to be 1.58% (95% CI: 1.28%‒1.94%). Of the detected AEs, 71.3% (95% CI: 62.1%‒80.5%) were avoidable. Additionally, 60.6% (95% CI: 50.7%‒70.5%) were categorized as mild, 31.9% (95% CI: 22.4%‒41.4%) as moderate, and 7.4% (95% CI: 2.1%‒12.7%) as severe. Primary care was the occurrence setting in 76.6% (95% CI: 68.0%‒85.2%) of cases. The overall incidence of AEs related to medication was 53.2% (95% CI: 50.9%‒55.5%). The most frequent types of AEs were prescription errors (28.7%; 95% CI: 19.5%‒37.9%), followed by drug administration errors by patients (17.0%; 95% CI: 9.4%‒24.6%), and clinical assessment errors (11.7%; 95% CI: 5.2%‒18.2%). The most common contributory factors were those related to the patient (80.6%; 95% CI: 71.1%‒90.1%) and tasks (59.7%; 95% CI: 48.0%‒71.4%). A high prevalence of AEs (1 in 66 consultations) was observed, which was slightly higher than that reported in similar studies. About 3 out of 4 such events were considered to be avoidable and 1 out of 13 was severe. Prescription errors, drug administration errors by patients, and clinical assessment errors were the most frequent types of AEs. Graphical Abstract., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care.)

Since the first description of Brugada syndrome (BrS), several studies were carried out aimed at diagnosis, arrhythmic risk stratification, and available strategies for sudden death prevention. In high-risk patients, the use of an implantable cardiac defibrillator was an evident option since the first description of the syndrome. Nevertheless, this strategy, while proven, as expected, to be effective in sudden death prevention, does not prevent arrhythmias and may not be an adequate or accepted solution for all patients. The need of a non-pharmacological therapy as a potential solution based on the electrophysiological mechanisms underlying the syndrome, led to search for substrate as target for catheter ablation. Advances in the tools, technology, and technical approach enabled to launch studies aimed at mapping the epicardium of patients with BrS in order to identify and ablate the substrate. As described in previous work and in our experience, an anatomically identifiable electrical substrate, which correspond to the typical ECG, is the ablation target. Complete substrate is better identified in a larger area with sodium-channel-blockers. Ablation of all abnormal electrical potentials is able to normalize the ECG and prevent arrhythmias induction. Encouraging preliminary data, if confirmed by longer follow-up and by multicentre randomized study, could change the whole therapeutic management in BrS patients., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The roles played by the peptides belonging to the tachykinin (neurokinin A and B) and calcitonin/calcitonin gene-related peptide (adrenomedullin, adrenomedullin 2, amylin, and calcitonin gene-related peptide (CGRP)) peptide families in cancer development are reviewed. The structure and dynamics of the neurokinin (NK)-2, NK-3, and CGRP receptors are studied together with the intracellular signaling pathways in which they are involved. These peptides play an important role in many cancers, such as breast cancer, colorectal cancer, glioma, lung cancer, neuroblastoma, oral squamous cell carcinoma, phaeochromocytoma, leukemia, bladder cancer, endometrial cancer, Ewing sarcoma, gastric cancer, liver cancer, melanoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal carcinoma, and thyroid cancer. These peptides are involved in tumor cell proliferation, migration, metastasis, angiogenesis, and lymphangiogenesis. Several antitumor therapeutic strategies, including peptide receptor antagonists, are discussed. The main research lines to be developed in the future are mentioned.

Purpose: Memory deficits are very frequent in patients with drug-resistant epilepsy, but they predict a small proportion of variance of their quality of life (QOL) in previous studies, possibly due to the lack of consideration of mediating factors of this relationship. This study aimed to examine whether trait anxiety mediates the relationship between memory and QOL in this population, controlling the influence of demographic and seizure-related factors., Methods: In this cross-sectional study, 119 adults with drug-resistant temporal lobe epilepsy (TLE) underwent a neuropsychological evaluation, in which memory, anxiety, and QOL were assessed., Results: In the total sample, better delayed memory had an effect on better QOL indirectly through lower trait anxiety (B = 0.13, SE = 0.06, p = 0.04, ab cs  = 0.13; κ 2  = 0.18; PM ind  = 0.76). Additionally, delayed memory has not a direct association with QOL (B = 0.04, SE = 0.09, p = 0.64, Cohen's f  2  = 0.005; PM dir  = 0.24), and the total effect of delayed memory on QOL tended to reach statistical significance (B = 0.17, SE = 0.10, p = 0.08). The proposed mediation model yielded excellent fit (CFI = 1.00, RMSEA = 0.0001, SRMR = 0.009, and χ 2 (1) = 0.50, p = 0.48) and explained 38% of the variance of QOL., Conclusion: These findings suggest that trait anxiety is an important factor in understanding the relationship between memory and QOL in patients with TLE, considering the influence of demographic and seizure-related variables, and may have relevant implications for decision-making in this population., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The objectives were: (a) to establish cannabis use prevalence in university students; (b) to determine the changes in consumption of cannabis between prior to and during lockdown. Problematic consumption, gender, and age were taken into account to establish risk groups. Of 1,472 participants between 18-54 years (M = 27.51), 8.01% reported using cannabis before and/or during lockdown (56.6% male). The Cannabis Abuse Screening Test (CAST) was used to detect cannabis abuse. The main form of consumption was spliffs (89.9%). The mean of spliffs consumed per day decreased during lockdown, but was only significant in male and in the 18-24 group. This decrease was also significant for all three levels of CAST problematic use. Users with moderate addiction and dependence reduced their average number of spliffs consumed per day during lockdown to a greater extent than those without addiction. These findings establish target groups of prevention interventions in the university., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Health misinformation about nutrition and other health aspects on social media is a current public health concern. Healthcare professionals play an essential role in efforts to detect and correct it. The present study focuses on analyzing the use of competencies associated with training in methodology, health literacy, and critical lecture in order to detect sources of health misinformation that use scientific articles to support their false information. A qualitative study was conducted between 15 and 30 January 2022, wherein the participants were recruited from active users from a nutrition conversation on Twitter, diets, and cancer and defined themselves as healthcare professionals. This study demonstrates that health literacy and critical lecture competencies allow for the detection of more misinformation messages and are associated with a high rate of responses to users that spread the misinformation messages. Finally, this study proposes the necessity of developing actions to improve health literacy and critical lecture competencies between healthcare professionals. However, in order to achieve this, health authorities must develop strategies to psychologically support those healthcare professionals faced with bullying as a result of their activity on social media debunking health hoaxes., Competing Interests: The authors declare no conflict of interest.

The objective was to analyze the relationship between depression and suicidal ideation and psychotropic drugs use during COVID-19 lockdown in adult population considering gender and age. The method used is a descriptive and non-probabilistic study, with a convenience sampling of 3780 participants (70.1% female), aged 18-64 years (M = 37.8). 18.3% participants presented depression and 5.1% exhibited suicidal ideation. The depression rate for female was double (21.4%) than male and 5 times higher (30.2%) for the youngest participants (18-24 years old) compared to oldest (55-64 years old), being this rate triple in suicidal ideation (9%). Depression correlated positively with tranquilizers and sleeping pills' consumption; and suicidal ideation did so with tranquilizers and sedatives. The rate of tranquilizer users was 8 times higher for severe depression compared to those who did not present depression, 5 times higher for sleeping pills, and 6 times higher for sedatives. The rate of tranquilizer users exhibiting suicidal ideation was more than triple than those who did not present suicidal ideation, between 3 and 4 times higher for sleeping pills, and almost 7 times higher for sedatives. The higher the level of depression and suicidal ideation during lockdown, the greater the consumption of psychotropic drugs. The consumption of psychotropic drugs should be monitored in people with depression and suicidal ideation during periods of crisis., Competing Interests: Conflicts of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Gambling addiction is increasing and is becoming a public health concern due to the rise of gambling-related harms affecting the youth. Previous studies suggest a strong link between problem gambling (PG) and substance use and psychosocial and familial factors. Our main objective was to analyze the association between PG and factors like sport, leisure-time activities, and risk-taking behaviors in adolescents. A survey on substance use and addictive behaviors was performed in 2019 on a representative sample of 2240 subjects (14-18 years) from the Southern Spain Region. Data variables like socio-demographic characteristics, sport, leisure and free time activities, family environment, PG (Lie-Bet Scale), compulsive internet use (CIUS Scale), and consumption of alcohol and cannabis were collected using a standardized questionnaire. Weighted PG prevalence was estimated in either sex, as well as the differences between various levels of PG using chi-square tests. Crude and adjusted weighted logistic regression models were used to identify predictors associated with PG. The prevalence of PG was associated with shopping frequency, compulsive internet use, cannabis use in the previous month, higher family economic status, and having a homemaker father which increased the likelihood of PG. On the contrary, cultural hobbies such as playing an instrument, painting, singing, and writing, and having a working mother were inversely associated with PG. Our results suggest that encouraging participation in creative activities along with supervised shopping and monitoring compulsive internet use and cannabis consumption may contribute some protection against adolescent PG., Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-022-00950-7., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2022.)

Women are more likely to use alcohol as a coping strategy for psychological distress, with higher rates of comorbidity with depression being found in those with an alcohol use disorder. The objective of this study was to analyze changes in problematic alcohol consumption and depression during the COVID-19 lockdown, and to establish a predictive model based on age. A total of 1889 women aged 18-64 years ( M  = 36.14) participated. The Patient Health Questionnaire was applied for depression, the Alcohol Use Disorders Identification Test-Short Version for alcohol, and active and avoidant coping were considered. In the period prior to the pandemic, depression and avoidant coping were good predictors of alcohol consumption in women, regardless of age. During lockdown, this predictive capacity was only maintained in women aged 35-64 years. In the mediational models, differences were observed according to age. For women aged 18-34 years, depression was the predictor variable of problematic alcohol consumption, but for women aged 35-64 years it was the avoidant coping style, which is the predominant style in women of this age with clinical depression. The relevance of age in the combined treatments of depression and problematic alcohol consumption is highlighted, and training in active coping strategies is suggested., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)